Pederin is the toxic compound found in the haemalymph of the staphylinid beetle, Paederus fuscipes. Its structure and stereochemistry were established in 1968. With its multiple functionality and nine chiral centers, it is by far the most complex (nonprotein) defensive substance to be isolated from an insect source. Aside from its vesicatory activity, pederin inhibits tumor growth (induced chemically in Lupinus albus, and with Sarcoma 180 in the mouse). Cultures of HeLa cells show almost complete disappearance of mitosis as well as other effects on exposure to solutions containing only 1 nanogram/ml. of pederin. Biochemical studies indicate that pederin inhibits its cytotoxic effects by blocking protein synthesis and, indirectly DNA synthesis. In this role, it is 1,000 to 10,000 times more active than the common antimetabolites. Pederin has also been shown to induce cell fusion in human skin fibroblasts. This project aims at the synthesis of pederin starting from a readily available chiral precursor, D-mannitol. The projected synthesis has as an especially attractive feature, the direct introduction of one chiral center (which would otherwise be very difficult to control) with the correct absolute stereochemistry. Model experiments which have already been carried out have been encouraging. We plan to prepare optically active pederin and pederin analogs for biological, biochemical, and possible medical experiments.